Non-viral transfection methods are increasingly used in both in vitro and in vivo systems for siRNA delivery. However, they have mixed results in difficult-to-transfect cells such as primary neuronal cells where chemical transfection typically yields can vary from 3-30% efficiency. Although multiple alternate transfection systems have made major strides, all have significant trade-off issues between transfection efficiency and viability. Thus, there is a continuing need for non-viral siRNA transfection methods and compositions that offer high transfection efficiency with little loss in cell viability, especially in typically difficult to transfect cell types.